The ?134.5 protein, present both in herpes simplex virus 1 and 2 (HSV), plays an essential role in viral virulence. Unlike wild-type virus, HSV mutants that lack the ?134.5 gene are incapable of replicating and causing diseases. However, the underlying mechanisms are not incompletely understood. The major goal of the proposed research is to investigate the biological functions of ?134.5 during HSV infection. HSV ?134.5 contains an amino-terminal domain, a linker region of triplet repeats, and a carboxyl- terminal domain. A critical function of ?134.5 is to block the interferon response mediated by double-stranded RNA dependent protein kinase PKR. In addition, ?134.5 is involved in virus egress. This activity maps to the amino-terminus of ?134.5 that shuttles between the nucleus, nucleolus and cytoplasm. It is thought that coordinated actions of functional elements in the ?134.5 protein and cellular factors facilitate virus egress that contributes to viral virulence. To test this hypothesis, mutational analysis will be performed to define functional modules of ?134.5. Recombinant viruses will be constructed to study viral replication, spread, and the interferon response in infected cells. Experiments will also be performed to identify targets of ?134.5. Furthermore, studies will be carried out to explore the molecular nature by which ?134.5 promotes viral infection. Taken together, these studies will provide insights into the mechanisms of HSV pathogenesis.
In summary, herpes simplex viruses are human pathogens that cause diseases such as genital herpes, keratitis, and encephalitis. This research is designed to investigate how a pathogenic factor of herpes simplex viruses facilitates viral infection, which may lead to the development of novel vaccines and antiviral therapeutics.
| Jin, Huali; Yan, Zhipeng; Ma, Yijie et al. (2011) A herpesvirus virulence factor inhibits dendritic cell maturation through protein phosphatase 1 and Ikappa B kinase. J Virol 85:3397-407 |
| Lei, Xiaobo; Liu, Xinlei; Ma, Yijie et al. (2010) The 3C protein of enterovirus 71 inhibits retinoid acid-inducible gene I-mediated interferon regulatory factor 3 activation and type I interferon responses. J Virol 84:8051-61 |
| Verpooten, Dustin; Feng, Zongdi; Valyi-Nagy, Tibor et al. (2009) Dephosphorylation of eIF2alpha mediated by the gamma134.5 protein of herpes simplex virus 1 facilitates viral neuroinvasion. J Virol 83:12626-30 |
